Magnolia Ariza-Nieto1, Joshua B Alley2, Sanjay Samy3, Laura Fitzgerald4, Francoise Vermeylen5, Michael L Shuler6, Jose O Aleman7. 1. M Ariza-Nieto, Research and Development, epiWELL, LLC, Ithaca, United States magnoliaariza@gmail.com. 2. J Alley, Donald Guthrie Foundation for Education and Research, Guthrie Clinic Sayre, Sayre, United States. 3. S Samy, Donald Guthrie Foundation for Education and Research, Guthrie Clinic Sayre, Sayre, United States. 4. L Fitzgerald, Donald Guthrie Foundation for Education and Research, Guthrie Clinic Sayre, Sayre, United States. 5. F Vermeylen, Cornell Statistical Consulting Unit, Cornell University, Ithaca, United States. 6. M Shuler, Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States. 7. J Aleman, Endocrinology, New York University Langone Medical Center, New York, United States.
Abstract
OBJECTIVE: We sought to discover secreted biomarkers to monitor the recovery of physiological adiponectin levels with metabolic surgery, focusing on epigenetic changes that might predict adiponectin function. DESIGN: We conducted a prospective observational study of patients undergoing metabolic surgery by Roux-en-Y gastric bypass (RYGB) for weight loss in a single center (IRB GHS # 1207-27). METHODS: All patients (n=33; 27 females; 6 males) signed informed consent. Metabolites, adiponectin, and miR-148a were measured in fasting plasma. We followed MIQE for transcript profiles. RESULTS: Patients lost on average 47±12% excess BMI (%EBMI) after 12 weeks. Adiponectin pre, post or delta [post minus pre] did not correlate with %EBMIL. A decrease in adiponectin following weight loss surgery was observed in a subset of patients, chi-square test of independence rejects the null hypotheses that the liver DNMT1 and delta adiponectin are independent (Chi-square statistics χ2 38 = 6.9205, P= 0.00852, n=33), as well as miR-148a and delta adiponectin are independent (Chisquare statistics χ2 40 = 9.6823, P= 0.00186, n=33). The presence of plasma miR-148a allows identification of patients that appear to be adiponectin insensitive at baseline. CONCLUSION: We combined the presence of plasma miR-148a, the concentration of total adiponectin and the expression of DNA methyltransferase 1 (DNMT1) in liver biopsy tissue to identify patients with non-physiological adiponectin. Weight loss and physical activity interventions complemented with the new method presented here could serve to monitor the physiological levels of adiponectin, thought to be important for long-term weight loss maintenance.
OBJECTIVE: We sought to discover secreted biomarkers to monitor the recovery of physiological adiponectin levels with metabolic surgery, focusing on epigenetic changes that might predict adiponectin function. DESIGN: We conducted a prospective observational study of patients undergoing metabolic surgery by Roux-en-Y gastric bypass (RYGB) for weight loss in a single center (IRB GHS # 1207-27). METHODS: All patients (n=33; 27 females; 6 males) signed informed consent. Metabolites, adiponectin, and miR-148a were measured in fasting plasma. We followed MIQE for transcript profiles. RESULTS: Patients lost on average 47±12% excess BMI (%EBMI) after 12 weeks. Adiponectin pre, post or delta [post minus pre] did not correlate with %EBMIL. A decrease in adiponectin following weight loss surgery was observed in a subset of patients, chi-square test of independence rejects the null hypotheses that the liver DNMT1 and delta adiponectin are independent (Chi-square statistics χ2 38 = 6.9205, P= 0.00852, n=33), as well as miR-148a and delta adiponectin are independent (Chisquare statistics χ2 40 = 9.6823, P= 0.00186, n=33). The presence of plasma miR-148a allows identification of patients that appear to be adiponectin insensitive at baseline. CONCLUSION: We combined the presence of plasma miR-148a, the concentration of total adiponectin and the expression of DNA methyltransferase 1 (DNMT1) in liver biopsy tissue to identify patients with non-physiological adiponectin. Weight loss and physical activity interventions complemented with the new method presented here could serve to monitor the physiological levels of adiponectin, thought to be important for long-term weight loss maintenance.
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